Metabolic model-based ecological modeling for probiotic design

Elife. 2024 Feb 21:13:e83690. doi: 10.7554/eLife.83690.

Abstract

The microbial community composition in the human gut has a profound effect on human health. This observation has lead to extensive use of microbiome therapies, including over-the-counter 'probiotic' treatments intended to alter the composition of the microbiome. Despite so much promise and commercial interest, the factors that contribute to the success or failure of microbiome-targeted treatments remain unclear. We investigate the biotic interactions that lead to successful engraftment of a novel bacterial strain introduced to the microbiome as in probiotic treatments. We use pairwise genome-scale metabolic modeling with a generalized resource allocation constraint to build a network of interactions between taxa that appear in an experimental engraftment study. We create induced sub-graphs using the taxa present in individual samples and assess the likelihood of invader engraftment based on network structure. To do so, we use a generalized Lotka-Volterra model, which we show has strong ability to predict if a particular invader or probiotic will successfully engraft into an individual's microbiome. Furthermore, we show that the mechanistic nature of the model is useful for revealing which microbe-microbe interactions potentially drive engraftment.

Keywords: B. longum; C. difficile; L. plantarum; computational biology; genome-scale metabolic modeling; microbiome; probiotics; systems biology.

MeSH terms

  • Gastrointestinal Microbiome*
  • Humans
  • Microbiota*
  • Probiotics*